A study of the safety, immunology, virology, and microbiology of adjunctive etanercept in HIV-1-associated tuberculosis

RS Wallis, P Kyambadde, JL Johnson, L Horter, R Kittle… - Aids, 2004 - journals.lww.com
RS Wallis, P Kyambadde, JL Johnson, L Horter, R Kittle, M Pohle, C Ducar, M Millard
Aids, 2004journals.lww.com
Objective: Tumor necrosis factor (TNF), an important inflammatory mediator in tuberculosis,
has been implicated in causing accelerated HIV disease progression in HIV-associated
tuberculosis. However, TNF blockade, particularly by monoclonal antibody, has been
associated with the reactivation of latent Mycobacterium tuberculosis infection by the
impairment of mycobacterial immunity. This phase 1 study examined the safety,
microbiology, immunology, and virology of TNF blockade using etanercept (soluble TNF …
Abstract
Objective:
Tumor necrosis factor (TNF), an important inflammatory mediator in tuberculosis, has been implicated in causing accelerated HIV disease progression in HIV-associated tuberculosis. However, TNF blockade, particularly by monoclonal antibody, has been associated with the reactivation of latent Mycobacterium tuberculosis infection by the impairment of mycobacterial immunity. This phase 1 study examined the safety, microbiology, immunology, and virology of TNF blockade using etanercept (soluble TNF receptor, Enbrel) during the initial treatment of HIV-associated tuberculosis.
Design:
A single-arm trial, with key endpoints compared with historical controls, conducted in Mulago Hospital, Kampala, Uganda.
Subjects:
Sixteen HIV-1-infected patients and 42 CD4-frequency-matched controls with sputum smear-positive tuberculosis and CD4 cell counts> 200 cells/μl.
Intervention:
Etanercept 25 mg, eight doses administered subcutaneously twice weekly beginning on day 4 of tuberculosis therapy.
Main outcome measures:
Serial examination, radiography, sputum culture, CD4 T-cell counts, plasma log 10 HIV-RNA copy numbers.
Results:
Trends towards superior responses to tuberculosis treatment were evident in etanercept-treated subjects in body mass, performance score, number of involved lung zones, cavitary closure, and time to sputum culture conversion. Etanercept treatment resulted in a 25% increase in CD4 cells by week 4 (P= 0.1 compared with controls). The change in CD4 cell count was inversely related to the change in serum neopterin, a marker of macrophage activation. There was no effect on plasma HIV RNA.
Conclusion:
Etanercept can be safely administered during the initial treatment of pulmonary tuberculosis. Further studies are warranted to examine the effects of etanercept on T-cell numbers, activation and apoptosis in AIDS and tuberculosis.
Lippincott Williams & Wilkins